Development of a novel six DNA damage response-related prognostic signature in osteosarcoma.

DNA damage response (DDR) plays a vital role in the development of cancer. Nevertheless, in osteosarcoma, the potential of DDR-related genes (DDRGs) remains unclear. Thus, the current research is intended to investigate the mechanisms of DDRGs in the development of osteosarcoma and to explore potential DDR-related biomarkers in forecasting the prognosis of osteosarcoma patients. The osteosarcoma genomic data from TCGA, GEO and cBioPortal databases were utilized for screening and identification of differentially expressed DDRGs (DEDDRGs). Consensus clustering analysis was performed to identify different subtypes of osteosarcoma based on the expressions of DDRGs. Key DEDRRGs were identified by overlapping DEDRRGs between different subtypes and DEDRRGs between tumor and control samples. Univariate, as well as LASSO regressions, were further applied to obtain robust prognostic signatures. GSVA and ssGSEA analysis were implemented to explore the underlying mechanisms of prognostic DDRG signature in regulating osteosarcoma. In addition, the drug sensitivity of patients in low- and high-risk groups was evaluated using pRRophetic algorithm. A total of 43 key DEDRRGs were identified. Followed by univariate Cox along with LASSO regression analyses, CDK6, CSF1R, EGFR, ERBB4, GATA3 and SOCS1 were identified as prognostic signatures in osteosarcoma. Cox regressions revealed that the risk score was an independent prognostic factor in osteosarcoma.  DDR may affect osteosarcoma via regulating immune microenvironment along with influencing cell proliferation, migration, adhesion and apoptosis. The chemotherapeutic response between patients in low- and high-risk groups was much different. The role of DDRGs in osteosarcoma and identified six DDR-linked biomarkers for forecasting the prognosis of osteosarcoma patients. Our outcomes enhanced the understanding of DDR-related molecular mechanisms involved in osteosarcoma and provided potential therapeutic targets for osteosarcoma patients.

Precursor-Directed Biosynthesis of Neoantimycin Derivatives with Selective Cytotoxicity.

A precursor-directed biosynthesis approach led to the accumulation of seven new neoantimycin derivatives (1-7) from Streptomyces conglobatus RJ2. Structure elucidation was conducted using NMR and HRESIMS analysis, and the absolute configuration was determined by advanced Marfey's method, Mosher's analysis, and ECD analysis. The obtained compounds revealed selective and significant cytotoxicity, specifically against colorectal cancer cells bearing the K-ras mutation, with IC50 values ranging from 40 nM to 3.5 µM.

Association of Different Types of Osteoarthritis with Different Immune-Related Subtypes and Hub Genes.

Background: Osteoarthritis (OA) is a diverse disorder that most frequently affects elderly people and makes them disabled. Many investigations have shown that the etiology of OA depends on cartilage wear, but immunology also plays a significant role. Thus, the goal of this study was to define the immune-related etiology of OA. Methods: Data from the "Gene Expression Omnibus (GEO)" database were used to find differentially expressed genes (DEGs), and the "Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm" was employed to calculate the quantity of distinct immune cells. We analyzed the results to identify patient subgroups and compare major active pathways. Results: The macrophage cell population accounts for the greatest percentage of infiltrating immune cells in OA. One hundred and twenty-two common intersection genes were identified, with the network analysis of protein-protein interactions revealing ten hub genes related to OA, including CXCL8, JUN, ATF3, DUSP1, PTGS2, IL6, MMP9, FOS, NFKBIA, and MYC. The random forest model showed that memory-activated CD4 T cells are strongly correlated with other immune cell types, while neutrophils have the weakest correlation with other immune cell types. Violin plots showed that OA patients had a significantly larger quantity of plasma cells and resting mast cells, with a significantly smaller quantity of resting memory CD4 T cells and activated mast cells than healthy controls. Conclusions: Two immune-related subgroups of OA were identified by semi-supervised clustering analysis of microarray data, and core genes were also determined by network analysis. A group of the immune infiltrating cells was selected by random forest analysis suggesting they are related to the pathogenesis of OA.

Coherent dual-frequency signal generation in an optoelectronic oscillator.

Coherent dual-frequency microwave signal generation using an optoelectronic oscillator (OEO) is presented and demonstrated. In the proposed OEO, a dual-band bandpass filter (DB-BPF) is utilized to select two oscillation modes. An external signal is injected into the OEO loop with its frequency equaling the frequency interval of the two oscillation modes. Owing to the modulation nonlinearity of the Mach-Zehnder modulator, the two oscillation frequencies interact with the injection frequency. When the phase and gain conditions are satisfied within the loop, injection locking between the two oscillation signals will be established, and their phases will be synchronized. The effect of gain competition in the OEO loop, which leads to single-frequency oscillation, is suppressed. An experiment is carried out, and two frequencies, of 16.083 GHz and 9.998 GHz, are generated at the same time. The phase noise values are -140.1 and -141.0 dBc/Hz @ 10 kHz, respectively. The coherence between the generated signals and sidemode suppression performance are evaluated.

18-Residue Peptaibols Produced by the Sponge-Derived Trichoderma sp. GXIMD 01001.

Seven new 18-residue peptaibols, trichorzins A-G (1-7), were isolated from the sponge-derived fungus Trichoderma sp. GXIMD 01001. Their structures and configurations were characterized by a comprehensive interpretation of the NMR spectroscopic data, MS/MS fragmentation, Marfey's method, and ECD analysis. The general sequences of trichorzins A-G are as follows: Ac-Aib1-Ala/Ser2-Ala3-Aib/Iva4-Iva5-Gln6-Aib/Iva7-Val/allo-Ile8-Aib9-Gly10-Leu11-Aib12-Pro13-Leu14-Aib15-Aib16-Gln17-Trpol/Pheol18. The obtained compounds were assessed for their potential antiproliferative and antimicrobial activities. All obtained compounds did not show potent antibacterial activity but exhibited significant cytotoxicity, with the lowest IC50 values at 0.46-4.7 µM against four human carcinoma cell lines.

An epipolythiodioxopiperazine alkaloid and diversified aromatic polyketides with cytotoxicity from the Beibu Gulf coral-derived fungus Emericella nidulans GXIMD 02509. / 北部湾珊瑚来源构巢裸胞壳菌GXIMD 02509ä¸­å ·æœ‰ç»†èƒžæ¯’æ€§çš„ä¸€ä¸ªå¤šç¡«ä»£äºŒé ®å“Œå—ªç”Ÿç‰©ç¢±å’Œç»“æž„å¤šæ ·çš„èŠ³é¦™èšé ®ç±»åŒ–åˆç‰©.

Marine microorganisms, especially marine fungi, have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites (Deshmukh et al., 2018; Carroll et al., 2022). The corals constitute a dominant part of reefs with the highest biodiversity, and harbor highly diverse and abundant microbial symbionts in their tissue, skeleton, and mucus layer, with species-specific core members that are spatially partitioned across coral microhabitats (Wang WQ et al., 2022). The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds, terpenes, alkaloids, peptides, aromatics, lactones, and steroids. They demonstrate a wide range of bioactivity such as anticancer, antimicrobial, and antifouling activity (Chen et al., 2022). The genetically powerful genus Emericella (Ascomycota), which has marine and terrestrial sources, includes over 30 species and is distributed worldwide. It is considered a rich source of diverse secondary metabolites with antimicrobial activity or cytotoxicity (Alburae et al., 2020). Notably, Emericella nidulans, the sexual state of a classic biosynthetic strain Aspergillus nidulans, was recently reported as an important source of highly methylated polyketides (Li et al., 2019) and isoindolone-containing meroterpenoids (Zhou et al., 2016) with unusual skeletons.

GRP78 Activity Moderation as a Therapeutic Treatment against Obesity.

Glucose-regulated protein 78 (GRP78), a molecular chaperone, is overexpressed in patients suffering from obesity, fatty liver, hyperlipidemia and diabetes. GRP78, therefore, can be not only a biomarker to predict the progression and prognosis of obesity and metabolic diseases but also a potential therapeutic target for anti-obesity treatment. In this paper, GRP78 inhibitors targeting its ATPase domain have been reviewed. Small molecules and proteins that directly bind GRP78 have been described. Putative mechanisms of GRP78 in regulating lipid metabolism were also summarized so as to investigate the role of GRP78 in obesity and other related diseases and provide a theoretical basis for the development and design of anti-obesity drugs targeting GRP78.

Penicixanthene E, a new xanthene isolated from a mangrove-derived fungus Penicillium sp.

One new xanthene derivative, named penicixanthene E (1), together with one known compound 2, was isolated from the EtOAc extract of the endophytic fungus Penicillium sp. GXIMD 03101, which was identified from the mangrove Acanthus ilicifolius L. collected in the South China Sea. The structure of 1 was elucidated by 1D and 2D NMR spectral interpretation and HREISMS data. The absolute configurations of C-9 and C-11 in 1 were proposed based on electronic circular dichroism (ECD), but the configuration at C-3 in 1 was unassigned. Compound 1 represents a xanthene derivative that was first reported, in which carbon-carbon double bond has been reduced. The cytotoxic activities of all compounds were evaluated, the result showed that compound 1 has weak activity against pancreatic cancer SW1990.

P38α MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation.

Estrogen and progesterone specify the establishment of uterine receptivity mainly through their respective nuclear receptors, ER and PR. PR is transcriptionally induced by estrogen-ER signaling in the endometrium, but how the protein homeostasis of PR in the endometrium is regulated remains elusive. Here, we demonstrated that the uterine-selective depletion of P38α derails normal uterine receptivity ascribed to the dramatic down-regulation of PR protein and disordered progesterone responsiveness in the uterine stromal compartment, leading to defective implantation and female infertility. Specifically, Ube3c, an HECT family E3 ubiquitin ligase, targets PR for polyubiquitination and thus proteasome degradation in the absence of P38α. Moreover, we discovered that P38α restrains the polyubiquitination activity of Ube3c toward PR by phosphorylating the Ube3c at serine741 . In summary, we provided genetic evidence for the regulation of PR protein stability in the endometrium by P38α and identified Ube3c, whose activity was modulated by P38α-mediated phosphorylation, as an E3 ubiquitin ligase for PR in the uterus.

New 3-Acyl Tetramic Acid Derivatives from the Deep-Sea-Derived Fungus Lecanicillium fusisporum.

Seven rare C3-C6 reduced 3-acyl tetramic acid derivatives, lecanicilliumins A-G (1-7), along with the known analogue cladosporiumin D (8), were obtained from the extract of the deep-sea-derived fungus Lecanicillium fusisporum GXIMD00542 within the family Clavipitacae. Their structures were elucidated by extensive spectroscopic data analysis, quantum chemistry calculations and chemical reaction. Compounds 1, 2, 5-7 exhibited moderate anti-inflammatory activity against NF-κB production using lipopolysaccharide (LPS) induced RAW264.7 cells with EC50 values range of 18.49-30.19 µM.

Phycocyanin Ameliorates Colitis-Associated Colorectal Cancer by Regulating the Gut Microbiota and the IL-17 Signaling Pathway.

Phycocyanin (PC) is a pigment-protein complex. It has been reported that PC exerts anti-colorectal cancer activities, although the underlying mechanism has not been fully elucidated. In the present study, azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice were orally administrated with PC, followed by microbiota and transcriptomic analyses to investigate the effects of PC on colitis-associated cancer (CAC). Our results indicated that PC ameliorated AOM/DSS induced inflammation. PC treatment significantly reduced the number of colorectal tumors and inhibited proliferation of epithelial cell in CAC mice. Moreover, PC reduced the relative abundance of Firmicutes, Deferribacteres, Proteobacteria and Epsilonbacteraeota at phylum level. Transcriptomic analysis showed that the expression of genes involved in the intestinal barrier were altered upon PC administration, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the IL-17 signaling pathway was affected by PC treatment. The study demonstrated the protective therapeutic action of PC on CAC.

Towards Accurate, Cost-Effective, Ultra-Low-Power and Non-Invasive Respiration Monitoring: A Reusable Wireless Wearable Sensor for an Off-the-Shelf KN95 Mask.

Respiratory rate is a critical vital sign that indicates health condition, sleep quality, and exercise intensity. This paper presents a non-invasive, ultra-low-power, and cost-effective wireless wearable sensor, which is installed on an off-the-shelf KN95 mask to facilitate respiration monitoring. The sensing principle is based on the periodic airflow temperature variations caused by exhaled hot air and inhaled cool air in respiratory cycles. By measuring the periodic temperature variations at the exhalation valve of mask, the respiratory parameters can be accurately and reliably detected, regardless of body movements and breathing pathways through nose or mouth. Specifically, we propose a voltage divider with controllable resistors and corresponding selection criteria to improve the sensitivity of temperature measurement, a peak detection algorithm with spline interpolation to increase sampling period without reducing the detection accuracy, and effective low-power optimization measures to prolong the battery life. The experimental results have demonstrated the effectiveness of the proposed sensor, showing a small mean absolute error (MAE) of 0.449 bpm and a very low power consumption of 131.4 µW. As a high accuracy, low cost, low power, and reusable miniature wearing device for convenient respiration monitoring in daily life, the proposed sensor holds promise in real-world feasibility.

Two new benzophenones isolated from a mangrove-derived fungus Penicillium sp.

One new benzophenone derivative, named penibenzophenone C (1), and a new benzophenone natural product, neamed penibenzophenone D (2), together with two known compounds (3, 4) were isolated from the EtOAc extract of the endophytic fungus Penicillium sp. isolated from the mangrove Acanthus ilicifolius L. collected in the South China Sea. The structures of 1-4 were elucidated by extensive NMR spectral interpretation and MS data. The new compounds 1 and 2 showed moderate antibacterial activities against methicillin-resistant Staphylococcus aureus with the MIC values of 3.12 and 6.25 µg ml-1, respectively.

Photonic approach for simultaneous measurement of microwave DFS and AOA.

A photonic scheme that can simultaneously estimate the microwave Doppler-frequency shift (DFS) and angle-of-arrive (AOA) is demonstrated. In the proposed system, the transmitted signal is independently mixed with two echo signals by a dual-channel microwave photonic mixer. By measuring the frequency of the intermediate frequency (IF) signal output from the two channels and the phase difference between them, the DFS (with direction identification) and AOA parameters can be obtained. In a proof-of-concept experiment, the errors are less than ${{\pm}}\;{0.08}\;{\rm{Hz}}$ for the DFS measurement within a range of ${\rm{\pm 100}}\;{\rm{kHz}}$ and less than ${\rm{\pm 1}.{3}}\deg$ for the AOA measurement ranging from 0° to 90°, respectively.

Modulation of Local Overactive Inflammation via Injectable Hydrogel Microspheres.

Although injectable hydrogel microsphere has demonstrated tremendous promise in clinical applications, local overactive inflammation in degenerative diseases could jeopardize biomaterial implantation's therapeutic efficacy. Herein, an injectable "peptide-cell-hydrogel" microsphere was constructed by covalently coupling of APETx2 and further loading of nucleus pulposus cells, which could inhibit local inflammatory cytokine storms to regulate the metabolic balance of ECM in vitro. The covalent coupling of APETx2 preserved the biocompatibility of the microspheres and achieved a controlled release of APETx2 for more than 28 days in an acidic environment. By delivering "peptide-cell-hydrogel" microspheres to a rat degenerative intervertebral disc at 4 weeks, the expression of ASIC-3 and IL-1ß was significantly decreased for 3.53-fold and 7.29-fold, respectively. Also, the content of ECM was significantly recovered at 8 weeks. In summary, the proposed strategy provides an effective approach for tissue regeneration under overactive inflammatory responses.

Marinoid J, a phenylglycoside from Avicennia marina fruit, ameliorates cognitive impairment in rat vascular dementia: a quantitative iTRAQ proteomic study.

CONTEXT: Fruit of Avicennia marina (Forsk.) Vierh. (Acanthaceae) is used as a Chinese herb. Studies have found that it contains marinoid J, a novel phenylethanoid glycoside (PG) compound, but its neuroprotective functions are largely unknown. OBJECTIVE: This study evaluated the effects of marinoid J on vascular dementia (VD) and determined its potential mechanisms of action. MATERIALS AND METHODS: The VD model was established by the ligation of the bilateral common carotid artery in Sprague-Dawley rats, who received daily intragastrically administration of saline, marinoid J (125 or 500 mg/kg body weight/d), or oxiracetam (250 mg/kg body weight/d) for 14 days (20 rats in each group). The Morris water maze (MWM) was used to evaluate cognitive performance. The hippocampus was subjected to histological and proteomic analyses. RESULTS: Marinoid J shortened the escape latency of VD rats (31.07 ± 3.74 s, p < 0.05). It also decreased malondialdehyde (MDA) (27.53%) and nitric oxide (NO) (20.41%) while increasing superoxide dismutase (SOD) (11.26%) and glutathione peroxidase (GSH-Px) (20.38%) content in hippocampus tissues. Proteomic analysis revealed 45 differentially expressed proteins (DEPs) in marinoid J-treated VD rats, which included angiotensin-converting enzyme (ACE), keratin 18 (KRT18), cluster of differentiation 34 (CD34), and synaptotagmin II (SYT2). CONCLUSIONS: Marinoid J played a role in protecting hippocampal neurons by regulating a set of proteins that influence oxidative stress and apoptosis, this effect may thereby alleviate the symptoms of VD rats. Thus, pharmacological manipulation of marinoid J may offer a novel opportunity for VD treatment.

Optical vector analysis with attometer resolution, 90-dB dynamic range and THz bandwidth.

Optical vector analysis (OVA) capable of achieving magnitude and phase responses is essential for the fabrication and application of emerging optical devices. Conventional OVA often has to make compromises among resolution, dynamic range, and bandwidth. Here we show an original method to meet the measurement requirements for ultra-wide bandwidth, ultra-high resolution, and ultra-large dynamic range simultaneously, based on an asymmetric optical probe signal generator (ASG) and receiver (ASR). The ASG and ASR remove the measurement errors introduced by the modulation nonlinearity and enable an ultra-large dynamic range. Thanks to the wavelength-independence of the ASG and ASR, the measurement range can increase by 2 N times by applying an N-tone optical frequency comb without complicated operation. In an experiment, OVA with a resolution of 334 Hz (2.67 attometer in the 1550-nm band), a dynamic range of > 90 dB and a measurement range of 1.075 THz is demonstrated.

Visual Object Tracking Based on Cross-Modality Gaussian-Bernoulli Deep Boltzmann Machines with RGB-D Sensors.

Visual object tracking technology is one of the key issues in computer vision. In this paper, we propose a visual object tracking algorithm based on cross-modality featuredeep learning using Gaussian-Bernoulli deep Boltzmann machines (DBM) with RGB-D sensors. First, a cross-modality featurelearning network based on aGaussian-Bernoulli DBM is constructed, which can extract cross-modality features of the samples in RGB-D video data. Second, the cross-modality features of the samples are input into the logistic regression classifier, andthe observation likelihood model is established according to the confidence score of the classifier. Finally, the object tracking results over RGB-D data are obtained using aBayesian maximum a posteriori (MAP) probability estimation algorithm. The experimental results show that the proposed method has strong robustness to abnormal changes (e.g., occlusion, rotation, illumination change, etc.). The algorithm can steadily track multiple targets and has higher accuracy.

Reconfigurable microwave photonic mixer with minimized path separation and large suppression of mixing spurs.

A compact reconfigurable photonic microwave mixer is proposed and demonstrated based on a dual-polarization Mach-Zehnder modulator and an optical 90-deg hybrid. By simply changing the photodetection schemes, single-ended, double-balanced, I/Q, and image-reject mixing can be implemented. Thanks to the sidebands selection by an optical filter, unwanted mixing spurs are highly suppressed. In addition, the system is insensitive to environmental vibration because the optical path separation is minimized. An experiment is carried out. Reconfigurable mixing functionalities with very small phase dithering are verified. The mixing spurs are suppressed by more than 30 dB, and the image-reject ratio for image-reject mixing is about 40 dB.

Deletion of the tyrosine phosphatase Shp2 in Sertoli cells causes infertility in mice.

The male's ability to reproduce is completely dependent on Sertoli cells. However, the mechanisms governing the functional integrity of Sertoli cells have remained largely unexplored. Here, we demonstrate that deletion of Shp2 in Sertoli cells results in infertility in mice. In Shp2 knockout mice (SCSKO), a normal population of Sertoli cells was observed, but the blood-testis barrier (BTB) was not formed. Shp2 ablation initiated the untimely and excessive differentiation of spermatogonial stem cells (SSCs) by disturbing the expression of paracrine factors. As a consequence, the process of spermatogenesis was disrupted, and the germ cells were depleted. Furthermore, Shp2 deletion impaired the cell junctions of the primary Sertoli cells and failed to support the clonal formation of SSCs co-cultured with SCSKO Sertoli cells. As expected, Shp2 restoration largely restores the cell junctions of the primary Sertoli cells and the clonal formation of SSCs. To identify the underlying mechanism, we further demonstrated that the absence of Shp2 suppressed Erk phosphorylation, and thus, the expression of follicle-stimulating hormone (FSH)- and testosterone-induced target genes. These results collectively suggest that Shp2 is a critical signaling protein that is required to maintain Sertoli cell function and could serve as a novel target for male infertility therapies.